DESCRIPTION: The purpose of this CDA-1 proposal is to provide Dr. Melissa Papesh with the support and mentorship necessary to make the transition from basic science research to clinical research of central auditory system dysfunction in Veterans. Specifically, her present proposal investigates the influence of exposure to high- intensity blast waves on the neural filtering of auditory information and the potential for blast-related neural dysfunction to contribute to difficulty understanding speech in noisy backgrounds. This proposal will provide Dr. Papesh with the tools and experience necessary to engage in clinical research and generate data which will be used in applying for future funding such as the CDA-2. The career plan is made up of coursework, publication and presentation of results, shadowing in mental health, and mentoring from Drs. Frederick Gallun, Curtis Billings, Robert Folmer, Marjorie Leek, and Bret Fuller. Blast-related injuries are the signature injuries of recent military conflicts, with estimates of up to 850,000 Veterans having suffered exposure to high-intensity blasts since 2002. A significant percentage of these Veterans suffer long term consequences affecting both sensory and cognitive function. Within the auditory domain, blast-exposed Veterans often report increased difficulty understanding speech in noisy environments, difficulty following long conversations, and decreased tolerance to environmental sound. Such complaints are common even when auditory thresholds are found to be normal, thus indicating a central source of dysfunction. Cognitive complaints of blast-exposed Veterans frequently include increased distractibility, poor selective and sustained attention, and poor memory and recall. Blast-related cognitive and sensory complaints may arise from a common source of neural dysfunction. The present research proposal investigates the hypothesis that blast exposure damages portions of the brain involved in the pre-attentive filtering of sensory information for relevant content. This process o filtering sensory information, also known as sensory gating, normally functions to protect higher cortical centers of the brain from being bombarded by irrelevant or redundant sensory information. This hypothesis is supported by numerous lines of evidence including the similarity between symptoms expressed by blast-exposed Veterans and those of populations known to have sensory gating impairments, data from clinical and animal studies indicating that blast exposure is likely to impact centers of the brain involved in sensory gating, and electroencephalographic (EEG) studies indicating that the brains of blast-exposed Veterans show a reduced ability to encode novel stimuli compared to neurologically normal participants. If sensory gating is impaired following blast exposure, this is likely to lead to difficulty with speeh understanding in noise due to an inability to devote neural resources to processing the speech stream of interest while filtering out irrelevant background noise. The present proposal investigates the extent to which blast exposure impairs sensory gating processes by using established auditory EEG protocols to assess sensory gating in blast-exposed Veterans and in a control group consisting of age- and hearing-matched previously-deployed Veterans with PTSD severity similar to the last-exposed Veteran group. This carefully matched control group will help to control for common comorbidities in the Veteran population which may otherwise confound test results. It is hypothesized that blast-exposed Veterans will display reduced ability to encode novel auditory information as well as increased neural representation of redundant and irrelevant auditory information compared to control participants. In addition, the relationship between speech-in-noise (SIN) understanding and sensory gating capacity will be investigated by comparing EEG measures of sensory gating with behavioral measures of SIN performance. A positive correlation between sensory gating capacity and SIN understanding is hypothesized such that those with poor sensory gating will also display poor performance on tests of speech understanding in noise.